Abstract Candidate's Career Goals: Dr. Han has a strong background in magnetic resonance (MR) imaging, image reconstruction and arterial spin labeling (ASL), with a Ph.D. in bio and brain engineering. Dr. Han is currently at a junior-faculty rank of instructor at Massachusetts General Hospital (MGH). His goal is to expand his future career to multi-modality positron emission tomography (PET)-MR imaging for translational research and clinical improvement. His long-term goal is to become an independent, accomplished investigator that can lead future scientific and clinical imaging projects taking full advantage of multi-modality PET-MR imaging. Career Development Plan: Foundational training in PET/PET-MR imaging as well as neurology is proposed for the candidate, an area that the candidate currently lacks knowledge and experience in. The candidate plans to engage in formal course work/seminars, research via one-on-one instructions with mentors and collaborators, conferences/presentations, manuscript/grant preparations, and teaching/leadership roles to grow as an independent investigator in the field of PET-MR imaging and neurology. Research Project: The overall goal of the proposed research is to take advantage of simultaneous dynamic PET and ASL-MR imaging to estimate the permeability surface product (PS) of the PET tracer, which is new physiological information that cannot be obtained with PET or MR alone. PS describes the unidirectional flux rate of macromolecules from the blood plasma into the interstitial space of cellular tissue and is the key metric for assessing the integrity of the blood-brain barrier (BBB). Knowing the PS of the PET tracer provides powerful capability to probe the physiological delivery process of essential macromolecules involved in the pathogenesis of diseases in relation to BBB, due to the theoretically unlimiting potential in the design of radioactive analogs of important biological compounds. We plan to develop a PET tracer PS mapping method, achieve the first phantom and human study with PS mapping, and study the changes in the spatial distribution of tau neurofibrillary tangles (tau) and amyloid-beta (A) plaque depositions in relation to the BBB integrity changes with pathological events associated with the progression of AD, by performing dynamic-PET/mPLD-ASL studies using 18F-T807 and 11C- Pittsburgh compound B (PiB) PET tracers on AD and normal subjects. Environment: MGH provides an ideal setting for conducting research in MR, PET, and PET-MR imaging since multiple state-of-the-art imaging systems are available for preclinical/clinical MR scanners and preclinical simultaneous PET-MR scanners. There is a dynamic flow phantom designed to simulate blood flow for two compartment pharmacokinetics and an MR-compatible pump and detection system for continuous blood sampling suitable for performing ASL flow and PET imaging studies with arterial sampling. Also, there is a shared memory supercomputer ideal for the image reconstruction proposed in the project. MGH is also home to many experts in both PET-MR imaging and neurology who can provide their expertise to this project.